Like the T822M variant, the G885R, P945S, A1045V, R1068H and G1077S variants, which are all located in the distal C-terminus beyond the cNBD (Figure 1), are novel HCN4 variants that Macri et al. [26] observed in their cohort of 527 unrelated individuals with early-onset AF (G885R, P945S and G1077S) or in their cohort of 443 referent individuals without history or ECG evidence of AF (A1045V and R1068H). This evidence concerns the gene HCN4 and atrial fibrillation.